Systems and methods for driving neural activity to control brain signaling and gene expression

Abstract

Methods for controlling brain activity in a subject are described herein. An example method can include delivering a stimulus to the subject, wherein the stimulus induces neural activity in the subject's brain and modulates expression of at least one soluble mediator of cellular activity (such as, for example, a cytokine, chemokine, and/or growth factor) within the subject, and the stimulus is delivered to the subject for less than one hour.

1 - 51 . (canceled) 
     
     
         52 . A method for controlling brain activity in a subject, comprising:
 delivering a plurality of stimuli to the subject, wherein each of the stimuli is delivered to the subject for less than about 30 minutes;   inducing, in response to each of the stimuli delivered to the subject, neural activity in the subject's brain;   modulating, in response to each of the stimuli delivered to the subject, expression of at least one soluble mediator of cellular activity within the subject; and   invoking, in response to each of the stimuli delivered to the subject, an immunomodulatory response in the subject, wherein each of the stimuli is a sensory flicker stimulus between about 20 Hz and 40 Hz.   
     
     
         53 . The method of  claim 52 , wherein the at least one soluble mediator of cellular activity comprise a cytokine, chemokine, or growth factor. 
     
     
         54 . The method of  claim 52 , wherein each of the stimuli is delivered to the subject for less than about 10 minutes. 
     
     
         55 . The method of  claim 54 , wherein each of the stimuli is delivered to the subject for less than about 5 minutes. 
     
     
         56 . The method of  claim 52 , wherein each of the stimuli is a non-invasive stimulus. 
     
     
         57 . The method of  claim 52 , wherein each of the stimuli is a 20 Hz sensory flicker stimulus. 
     
     
         58 . The method of  claim 52 , wherein each of the stimuli is a 40 Hz sensory flicker stimulus. 
     
     
         59 . The method of  claim 52 , wherein each of the stimuli is at least one of a visual or auditory stimulus. 
     
     
         60 . The method of  claim 52 , wherein each of the stimuli is a combined visual and auditory stimulus. 
     
     
         61 . The method of  claim 52 , further comprising:
 selecting a soluble mediator of cellular activity to modulate, wherein the at least one soluble mediator includes the selected soluble mediator; and   selecting a stimulation protocol that modulates the selected soluble mediator of cellular activity, wherein each of the stimuli is delivered according to the selected stimulation protocol.   
     
     
         62 . The method of  claim 52 , wherein each of the stimuli comprises a 40 Hz sensory flicker stimulus, and wherein the at least one soluble mediator of cellular activity comprises Interleukin-4 (IL-4), Interleukin-7 (IL-7), Granulocyte-macrophage colony-stimulating factor (GM-CSF), Interleukin-12 p70 (IL-12p70), Interleukin-12 p40 (IL-12p40), Interferon-γ (IFN-γ), LIF, Tumor necrosis factor-α (TNF-α), Macrophage inflammatory protein 1β (MIP-1β), monokine induced by gamma interferon (MIG), growth-regulated oncogene-α (GRO-α), LIX (CXCL5), granulocyte colony-stimulating factor (G-CSF), Interleukin-1β (IL-1β), Interleukin-3 (IL-3), Interleukin-6 (IL-6), Interleukin-15 (IL-15), Regulated upon Activation, Normal T cell Expressed, and Secreted (RANTES), macrophage colony-stimulating factor (M-CSF), Interleukin-13 (IL-13), monocyte chemoattractant protein 1 (MCP-1), and/or Interleukin-1α(IL-1α), and/or Eotaxin. 
     
     
         63 . The method of  claim 52 , wherein each of the stimuli comprises a 40 Hz sensory flicker stimulus or a random sensory flicker stimulus, and wherein the at least one soluble mediator of cellular activity comprises monokine induced by gamma interferon (MIG), growth-regulated oncogene-α (GRO-α), LIX (CXCL5), granulocyte colony-stimulating factor (G-CSF), Interleukin-1β (IL-13), Interleukin-3 (IL-3), Interleukin-6 (IL-6), Interleukin-15 (IL-15), Regulated upon Activation, Normal T cell Expressed, and Secreted (RANTES), and/or macrophage colony-stimulating factor (M-CSF). 
     
     
         64 . The method of  claim 52 , wherein each of the stimuli comprises a 40 Hz sensory flicker stimulus or a constant sensory stimulus, and wherein the at least one soluble mediator of cellular activity comprises Interleukin-13 (IL-13), monocyte chemoattractant protein 1 (MCP-1), and/or Interleukin-1α(IL-1α). 
     
     
         65 . The method of  claim 52 , wherein each of the stimuli comprises a 20 Hz sensory flicker stimulus, and wherein the at least one soluble mediator of cellular activity comprises Interleukin-4 (IL-4), Interleukin-7 (IL-7), Granulocyte-macrophage colony-stimulating factor (GM-CSF), Interleukin-12 p70 (IL-12p70), Interleukin-12 p40 (IL-12p40), Interferon-γ (IFN-γ), LIF, Tumor necrosis factor-α (TNF-α), Macrophage inflammatory protein 1β (MIP-1β), Eotaxin, Interleukin-10 (IL-10), vascular endothelial growth factor (VEGF), Interleukin-2 (IL-2), Interleukin-5 (IL-5), Interleukin-9 (IL-9), Macrophage inflammatory protein 1α (MIP-1α), monokine induced by gamma interferon (MIG), growth-regulated oncogene-α (GRO-α), LIX (CXCL5), granulocyte colony-stimulating factor (G-CSF), Interleukin-1β (IL-1β), Interleukin-3 (IL-3), Interleukin-6 (IL-6), Interleukin-15 (IL-15), Regulated upon Activation, Normal T cell Expressed, and Secreted (RANTES), macrophage colony-stimulating factor (M-CSF), Interleukin-13 (IL-13), monocyte chemoattractant protein 1 (MCP-1), and/or Interleukin-1α(IL-1α). 
     
     
         66 . The method of  claim 52 , wherein the brain activity is induced in at least one of the sensory cortices. 
     
     
         67 . The method of  claim 52 , wherein the brain activity is induced in at least one of the hippocampus, medial temporal lobes, frontal lobes, subcortical structures, thalamus, hypothalamus, or brainstem. 
     
     
         68 . The method of  claim 52 , wherein each of the stimuli drives neural activity in the subject's brain. 
     
     
         69 . The method of  claim 68 , wherein the neural activity in the subject's brain is neural activity in a range between about 20 and 40 Hz. 
     
     
         70 . The method of  claim 52 , further comprising treating at least one of disease, injury, infection, or normal aging in the subject's brain using each of the stimuli delivered to the subject. 
     
     
         71 . The method of  claim 52 , wherein the method comprises treating a neurodegenerative disease using each of the stimuli delivered to the subject. 
     
     
         72 . The method of  claim 71 , wherein the neurodegenerative disease is Alzheimer's disease, Parkinson's disease, dementia, frontotemporal dementia, vascular dementia, amyotrophic lateral sclerosis (ALS), or multiple sclerosis (MS). 
     
     
         73 . The method of  claim 52 , wherein the method comprises treating a condition in the subject by modulating at least one of immunomodulatory signaling or cell survival signaling within the subject. 
     
     
         74 . The method of  claim 73 , wherein the condition is epilepsy, schizophrenia, autism, traumatic brain injury (TBI), bipolar disorder, stroke, or depression. 
     
     
         75 . The method of  claim 52 , wherein the method comprises inducing or suppressing neuroplasticity of the subject's brain using each of the stimuli delivered to the subject. 
     
     
         76 . The method of  claim 52 , wherein each of the stimuli upregulates at least one intracellular signaling pathway. 
     
     
         77 . The method of  claim 76 , wherein the at least one intracellular signaling pathway comprises a canonical kinase pathway. 
     
     
         78 . The method of  claim 76 , wherein the at least one intracellular signaling pathway comprises mitogen activated protein kinase (MAPK) pathway, nuclear factor kappa-light-chain-enhancer of activated B cells (NFκB) pathway, Cyclooxygenase-2 (COX-2) pathway, Nuclear factor (erythroid-derived 2)-like 2 (Nrf2) pathway, Phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K)/Akt pathway, or Janus kinase (JAK)-Signal Transducer and Activator of Transcription (STAT) pathway. 
     
     
         79 . The method of  claim 52 , wherein each of the stimuli effects on intracellular signaling modulate expression or activity of at least one immediate early gene. 
     
     
         80 . The method of  claim 79 , wherein the at least one immediate early gene is activity-regulated cytoskeleton-associated protein (ARC) or Fos proto-oncogene (C-Fos). 
     
     
         81 . The method of  claim 52 , wherein each of the stimuli modulates intracellular signaling that regulates differentiation. 
     
     
         82 . A method of treating a neurological condition in a subject, comprising:
 exposing the subject to a plurality of stimuli, wherein each of the stimuli is delivered to the subject for less than about 30 minutes;   inducing, in response to each of the stimuli exposed to the subject, neural activity in the subject's brain; and   modulating, in response to each of the stimuli exposed to the subject, expression of at least one soluble mediator of cellular activity within the subject, wherein each of the stimuli is a sensory flicker stimulus between about 20 Hz and 40 Hz.   
     
     
         83 . The method of  claim 82 , wherein the neurological condition comprises Schizophrenia, Epilepsy, Frontotemporal dementia, vascular dementia, Bipolar disorder, Parkinson's disease, Alzheimer's disease, Amyotrophic Lateral Sclerosis, Stroke, Traumatic brain injury, Multiple sclerosis, or Depression. 
     
     
         84 . The method of  claim 82 , wherein the neurological condition is depression. 
     
     
         85 . The method of  claim 82 , wherein the neurological condition comprises inflammatory damage resulting from aging, traumatic brain injury, stress, schizophrenia, and/or depression.